No DVT Advantage for Dalteparin

Action Points

Note that in this study conducted among critically ill patients, dalteparin, a low-molecular-weight heparin, as compared with unfractionated heparin, did not decrease the incidence of proximal deep-vein thrombosis.

Point out, however, that there was a significant reduction in the secondary end point of pulmonary embolism in the dalteparin group. The reasons for the reduction in PEs despite there being no significant difference in DVTs are not known.

Use of the low molecular weight heparin dalteparin was not found to be superior to unfractionated heparin for preventing deep vein thrombosis (DVT) in critically ill patients, according to a multicenter study.

Among the more than 3,700 patients in the trial, 5.1% of those receiving dalteparin developed proximal DVTs, as did 5.8% of those given unfractionated heparin (HR for dalteparin 0.92, 95% CI 0.68 to 1.23, P=0.57), according to Deborah Cook, MD, of McMaster University in Hamilton, Ont., and colleagues.

"The confidence interval around the hazard ratio for the primary end point was fairly wide, so it did not exclude either a 32% benefit or a 23% harm associated with dalteparin, as compared with unfractionated heparin. Thus, the result for the primary outcome was not clinically directive," Cook and co-authors wrote online in the New England Journal of Medicine.

Previous trials of thromboprophylaxis in critically ill patients, who are at high risk because of their illness, sedation, paralysis, and central venous catheterization, have been inconclusive.

In an attempt to clarify the relative benefits of unfractionated heparin and low molecular weight heparin, the investigators randomized 3,764 patients to subcutaneous dalteparin, 5,000 IU once per day, or unfractionated heparin, 5,000 IU twice per day.

Although the primary outcome was not met, on a secondary outcome measure -- the incidence of pulmonary embolism -- patients treated with dalteparin had a significantly lower incidence of PEs (1.3% versus 2.3%, HR 0.51, 95% CI 0.30 to 0.88, P=0.01), the investigators reported.

There also was a nonsignificant trend toward a lower rate of another composite secondary endpoint -- any venous thromboembolism or death -- for those patients treated with dalteparin (28.3% versus 31.4%, HR 0.89, 95% CI 0.79 to 1.01, P=0.07).

Rates of catheter-related thrombosis and DVTs in sites other than the lower leg did not differ between the groups, nor did the incidence of major bleeds or heparin-induced thrombocytopenia, Cook's group reported.

In a per-protocol analysis, however, thrombocytopenia occurred less frequently with dalteparin, but the investigators advised against drawing conclusions from secondary outcomes.

The investigators used screening compression ultrasonography for diagnosis in the study, which they acknowledged has limitations.

Potential reasons for why there was a significant difference in rates of PEs but not in DVTs included the possibility of emboli from other sites such as the arms or pelvis or thrombus formation in the pulmonary arteries.

The investigators noted that the study outcome might have been different if they had chosen other drugs or different doses.

And although they found no significant difference on the primary endpoint, they concluded, "It is possible that in a larger trial, such a difference might have been detected."

The study was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, and the Australian and New Zealand College of Anesthetists Research Foundation.

Several of the investigators disclosed receiving consulting fees and grant support from multiple companies, including Pfizer, Boehringer Ingelheim, sanofi-aventis, GlaxoSmithKline, and Bayer Healthcare.

One also is on advisory boards for Pfizer and Alexion and has received payment for developing educational presentations and travel from Pfizer.

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